The precise role(s) of cytokines in autoimmune diseases is still being investigated. Several proinflammatory actions of TNF may contribute to its role in the pathogenesis of RA; in addition to stimulating the release of other proinflammatory cytokines, including IL-6, IL-8, IL-1', and leukemia-inhibitory factor (LIF), TNA6 induces the release of proteases from neutrophils, fibroblasts, and chondrocytes. TNF6 also induces expression of endothelial adhesion molecules, which lead to rapid transmigration of leukocytes into extravacular sites. Clinical trials in RA patients using monoclonal antibodies to TNF and soluble TNF reeptor fusion proteins have demonstrated remarkable positive clinical improvements in short term trials. The name of the investigational drug is Recombinant Methionyl Human Tumor Necrosis Fctor Binding Protein PEGylated Dimer (TNFbp Dimer). The primary objectives of this study are to evaluate the safety, immunogenicity and pharmacokinetics and potential efficacy of intravenous administration of TNFbp Dimer in patients with moderate to severe active rheumatoid arthritis (RA). This will include an assessment of the effect of antibody generation on the clearance of TNFbp Dimer. Thirty-six patients (9/group) will receive either placebo, 30, 100, or 300 5g/kg of the TNF bp dimer. Infusions will occur at baseline, 3 and 6 weeks. Patients will be screened for eligibility; if eligible, they will proceed through the treatment phase receiving their first IV infusion on day 0. Patients wil be admitted to the GCRC 24 hours before and after each IV infusion. Outpatient clinic visits will be 3, 5, 7, 14 and 21 days after each IV. The termination visit will be 77 days after the first IV infusion, for patients who complete the study. UAB is the leading center for this phase I/II study.